Data Fail to Support Thimerosal-Autism Link

Action Points

Discuss with parents that data from a recent case control study indicates no increased risk of autism from prenatal and infant vaccination with thimerosal-containing vaccines.

Further discuss with parents that this latest study adds to data collected from four previous studies, all of which fail to demonstrate any connection between the development of autism and prior exposure to thimerosal-containing vaccines.

Yet another study -- this one analyzing insurance claims data and other records for children with autism spectrum disorders -- showed that exposure to thimerosal, either prenatally or after birth, did not increase the risk of autism, researchers said.

The case-control study, of 256 children with autism spectrum disorders and 752 age- and sex-matched healthy controls, found that higher-than-average exposures to ethylmercury were, if anything, less common in kids with autism compared with healthy kids, reported Frank DeStefano, MD, MPH, of the CDC's Immunization Safety Office in Atlanta, and colleagues.

The study of thimerosal exposures, conducted among children belonging to three managed care organizations, was published in the journal Pediatrics. It was the latest of a number of studies that found no link between thimerosal and autism.

The research team found the following odds ratios for autism spectrum disorders associated with increases in ethylmercury exposure of two standard deviations, after adjusting for numerous potential confounders such as birth weight and maternal age:

Prenatal exposure: OR 1.12 (95% CI 0.83 to 1.51)

Exposure from birth to 1 month of age: OR 0.88 (95% CI 0.62 to 1.26)

Exposure from birth to 7 months: OR 0.60 (95% CI 0.36 to 0.99)

Exposure from birth to 20 months: OR 0.60 (95% CI 0.32 to 0.97)

Noting that increased ethylmercury exposure in the two longer postnatal periods actually appeared to decrease the risk of three autism spectrum disorder outcomes, DeStefano and colleagues wrote that they were "not aware of a biological mechanism that would lead to this result."

But they were sure of one thing: the data yielded "no evidence that increasing ethylmercury exposure from thimerosal-containing immunoglobulins was associated with increased risk of autism spectrum disorders, autistic disorder, or [spectrum disorders] with regression."

The analysis is the latest in a long parade of studies, using a variety of methods and data sources, to find no connection between vaccines containing thimerosal (once commonly used as a preservative) and autism.

The flap over thimerosal and autism led vaccine manufacturers to remove the preservative from most of their products by 2001. Yet new autism diagnoses have soared since then, whereas a decrease in autism would be expected if thimerosal was an important cause of the condition.

Although the connection is now widely discredited, DeStefano and colleagues had access to an unusually detailed dataset that could more firmly establish whether or not such a link could exist.

Not only did the researchers have immunization records for the children, but they also had direct access to the children for in-person assessments and to their mothers for interviews to establish prenatal exposures and other potentially relevant factors.

The participants chosen for analysis were born from 1994 to 1999 and were continuously enrolled in the three managed care organizations from birth through 24 months of age, as well as currently enrolled when the analysis was conducted. At that time, the children were 6 to 13 years old.

Ethylmercury exposures were calculated from computerized immunization records and review of medical charts. The mercury content of each vaccine dose was obtained from lot-specific manufacturers' records and published data. Prenatal exposures were calculated from mothers' receipt of immunoglobulins, tetanus toxoids, and diphtheria-tetanus immunizations during pregnancy.

Average cumulative ethylmercury exposure for the four periods (prenatal, birth to 1 month, birth to 7 months, and birth to 20 months) was nearly identical in every comparison between cases and controls.

Although there was no increase in the risk for autism spectrum disorders as a group with increased mercury exposure, DeStefano and colleagues also looked at whether there might be a specific relationship with autistic disorder or spectrum disorders with regression.

The analysis of 187 children with an autistic disorder and of the 49 with autism spectrum disorders with regression showed the same patterns as in the larger group.

In fact, in the latter group, the decreased risk seen with increased ethylmercury exposure over 7 and 20 months after birth was especially pronounced.

Comparing these 49 children with 652 age- and sex-matched controls produced odds ratios of 0.21 (95% CI 0.08 to 0.60) for exposures from birth to 7 months and 0.30 (95% CI 0.08 to 0.76) for exposures from birth to 20 months.

"No single study can definitively establish or disprove the hypothesis that thimerosal exposure increases the risk of autism spectrum disorders," DeStefano and colleagues pointed out, given that randomized trials would be unethical.

On the other hand, they noted that a 2004 review by the Institute of Medicine involving multiple studies concluded that the link between autism and thimerosal was unsupported -- and four additional studies using different methodologies also failed to demonstrate any connection.

DeStefano and colleagues did identify several limitations of their own study: the possibility of unmeasured confounding factors, potential recall and reporting bias in the maternal interviews, and the uncertainty inherent in diagnoses of autism spectrum disorders.

The study was supported by a contract from the CDC to America's Health Insurance Plans and via America's Health Insurance Plans subcontracts to the authors' institutions.

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